DE602004011401T2 - Benzazepinderivate als histamin-h3-antagonisten - Google Patents
Benzazepinderivate als histamin-h3-antagonisten Download PDFInfo
- Publication number
- DE602004011401T2 DE602004011401T2 DE602004011401T DE602004011401T DE602004011401T2 DE 602004011401 T2 DE602004011401 T2 DE 602004011401T2 DE 602004011401 T DE602004011401 T DE 602004011401T DE 602004011401 T DE602004011401 T DE 602004011401T DE 602004011401 T2 DE602004011401 T2 DE 602004011401T2
- Authority
- DE
- Germany
- Prior art keywords
- tetrahydro
- benzazepin
- cyclobutyl
- carboxamide
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000008038 benzoazepines Chemical class 0.000 title abstract description 10
- 239000003395 histamine H3 receptor antagonist Substances 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 5
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 5
- -1 cyano, amino Chemical group 0.000 claims description 255
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 8
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 7
- KUAAYUVPTOBMTO-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-iodobenzamide Chemical compound C1=CC(I)=CC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 KUAAYUVPTOBMTO-UHFFFAOYSA-N 0.000 claims description 7
- ZMLFHUQJQMJDSS-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-methylpyridine-3-carboxamide Chemical compound CC1=NC=CC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 ZMLFHUQJQMJDSS-UHFFFAOYSA-N 0.000 claims description 6
- MOCFLVWSVKSXBB-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-pyridin-2-ylbenzamide Chemical compound C=1C=C(C=2N=CC=CC=2)C=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 MOCFLVWSVKSXBB-UHFFFAOYSA-N 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 5
- LJCMUXJHFLBZBS-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-6-oxo-1h-pyrazine-3-carboxamide Chemical compound C1=NC(O)=CN=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 LJCMUXJHFLBZBS-UHFFFAOYSA-N 0.000 claims description 5
- NVNOFQASRHGVIL-UHFFFAOYSA-N 4-cyano-n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)benzamide Chemical compound C=1C=C(C#N)C=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 NVNOFQASRHGVIL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003435 aroyl group Chemical group 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- OBNXXQOCUBBNJQ-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-(1,2,4-triazol-1-yl)benzamide Chemical compound C=1C=CC(N2N=CN=C2)=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 OBNXXQOCUBBNJQ-UHFFFAOYSA-N 0.000 claims description 4
- SZQVBAQOGJHVNN-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-pyrazol-1-ylbenzamide Chemical compound C=1C=CC(N2N=CC=C2)=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 SZQVBAQOGJHVNN-UHFFFAOYSA-N 0.000 claims description 4
- FYIZBSFFBVQFJB-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-pyridin-4-ylbenzamide Chemical compound C=1C=C(C=2C=CN=CC=2)C=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 FYIZBSFFBVQFJB-UHFFFAOYSA-N 0.000 claims description 4
- ISYDKRUHEKEWFT-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)methanesulfonamide Chemical compound C1CC2=CC(NS(=O)(=O)C)=CC=C2CCN1C1CCC1 ISYDKRUHEKEWFT-UHFFFAOYSA-N 0.000 claims description 4
- IAZKDBYKNDKJHG-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)morpholine-4-carboxamide Chemical compound C1COCCN1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 IAZKDBYKNDKJHG-UHFFFAOYSA-N 0.000 claims description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- VVEZSYWEXMIOOF-UHFFFAOYSA-N 2-(2,1,3-benzoxadiazol-5-yl)-n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,3-thiazole-4-carboxamide Chemical compound C=1SC(C2=CC3=NON=C3C=C2)=NC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 VVEZSYWEXMIOOF-UHFFFAOYSA-N 0.000 claims description 3
- SOHNDBTVKBBZQE-UHFFFAOYSA-N 3-cyclopropyl-1,2,4,5-tetrahydro-3-benzazepin-7-amine Chemical compound C1CC2=CC(N)=CC=C2CCN1C1CC1 SOHNDBTVKBBZQE-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- PZIVOFLYUOOSSN-UHFFFAOYSA-N 5-bromo-n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)pyridine-3-carboxamide Chemical compound BrC1=CN=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1 PZIVOFLYUOOSSN-UHFFFAOYSA-N 0.000 claims description 3
- SRFREXFOLLXNSB-UHFFFAOYSA-N 6-(4-cyanophenyl)-n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)pyridine-3-carboxamide Chemical compound C=1C=C(C=2C=CC(=CC=2)C#N)N=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 SRFREXFOLLXNSB-UHFFFAOYSA-N 0.000 claims description 3
- QFRYSWFHAXSCHN-UHFFFAOYSA-N 6-cyano-n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)pyridine-3-carboxamide Chemical compound C=1C=C(C#N)N=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 QFRYSWFHAXSCHN-UHFFFAOYSA-N 0.000 claims description 3
- 125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 3
- 125000005533 aryl carboxamido group Chemical group 0.000 claims description 3
- 125000005421 aryl sulfonamido group Chemical group 0.000 claims description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- HKPJOESQIRCIQC-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,2,5-oxadiazole-3-carboxamide Chemical compound C1=NON=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 HKPJOESQIRCIQC-UHFFFAOYSA-N 0.000 claims description 3
- XSRDKYGTWDCLKE-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,2,5-thiadiazole-3-carboxamide Chemical compound C1=NSN=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 XSRDKYGTWDCLKE-UHFFFAOYSA-N 0.000 claims description 3
- SZLCURRAMPGOAI-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,2-oxazole-3-carboxamide Chemical compound C1=CON=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 SZLCURRAMPGOAI-UHFFFAOYSA-N 0.000 claims description 3
- PMRRXSKVYJQKOV-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,3-thiazole-4-carboxamide Chemical compound C=1SC=NC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 PMRRXSKVYJQKOV-UHFFFAOYSA-N 0.000 claims description 3
- FPRLBVXOHMHEDF-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1,5-dimethylpyrazole-3-carboxamide Chemical compound CN1C(C)=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=N1 FPRLBVXOHMHEDF-UHFFFAOYSA-N 0.000 claims description 3
- AIJYSVWXGGTEHO-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1-methylimidazole-4-carboxamide Chemical compound CN1C=NC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1 AIJYSVWXGGTEHO-UHFFFAOYSA-N 0.000 claims description 3
- PWNZSMRHWCAIGN-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-1-methyltriazole-4-carboxamide Chemical compound N1=NN(C)C=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 PWNZSMRHWCAIGN-UHFFFAOYSA-N 0.000 claims description 3
- VYLJHDIOYIACOW-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2,5-dimethylfuran-3-carboxamide Chemical compound O1C(C)=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1C VYLJHDIOYIACOW-UHFFFAOYSA-N 0.000 claims description 3
- ZWMRPALYQUTCSP-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-(trifluoromethyl)-1,8-naphthyridine-3-carboxamide Chemical compound FC(F)(F)C1=NC2=NC=CC=C2C=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 ZWMRPALYQUTCSP-UHFFFAOYSA-N 0.000 claims description 3
- IGFFMWRNMSGGMF-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-ethylbutanamide Chemical compound C1CC2=CC(NC(=O)C(CC)CC)=CC=C2CCN1C1CCC1 IGFFMWRNMSGGMF-UHFFFAOYSA-N 0.000 claims description 3
- DDRXDOAFAFTRBV-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-methyl-1,6-naphthyridine-3-carboxamide Chemical compound CC1=NC2=CC=NC=C2C=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 DDRXDOAFAFTRBV-UHFFFAOYSA-N 0.000 claims description 3
- QISMYZFJFXMDTI-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-methyl-1,8-naphthyridine-3-carboxamide Chemical compound CC1=NC2=NC=CC=C2C=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 QISMYZFJFXMDTI-UHFFFAOYSA-N 0.000 claims description 3
- YRRDXFPNHICWSL-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-methyl-5-phenylfuran-3-carboxamide Chemical compound CC=1OC(C=2C=CC=CC=2)=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 YRRDXFPNHICWSL-UHFFFAOYSA-N 0.000 claims description 3
- NCUNJYOXIUGEEX-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-methylbenzamide Chemical compound CC1=CC=CC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 NCUNJYOXIUGEEX-UHFFFAOYSA-N 0.000 claims description 3
- LNMOMZRDMIOXIB-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-methylfuran-3-carboxamide Chemical compound O1C=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1C LNMOMZRDMIOXIB-UHFFFAOYSA-N 0.000 claims description 3
- XRVJZSHMNLEDFL-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-phenyl-1,3-thiazole-4-carboxamide Chemical compound C=1SC(C=2C=CC=CC=2)=NC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 XRVJZSHMNLEDFL-UHFFFAOYSA-N 0.000 claims description 3
- DEGIPYMSDPFESD-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2-phenyltriazole-4-carboxamide Chemical compound C1=NN(C=2C=CC=CC=2)N=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 DEGIPYMSDPFESD-UHFFFAOYSA-N 0.000 claims description 3
- QARDHTVKTWCYFA-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-2h-benzotriazole-5-carboxamide Chemical compound C=1C=C2NN=NC2=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 QARDHTVKTWCYFA-UHFFFAOYSA-N 0.000 claims description 3
- KMOZQOQSKRBXLU-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-fluorobenzamide Chemical compound FC1=CC=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1 KMOZQOQSKRBXLU-UHFFFAOYSA-N 0.000 claims description 3
- PXQRLKDUBRZYTO-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-methyl-1,2-oxazole-5-carboxamide Chemical compound O1N=C(C)C=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 PXQRLKDUBRZYTO-UHFFFAOYSA-N 0.000 claims description 3
- RRPUNCUXXIJQHN-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-methylbenzamide Chemical compound CC1=CC=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1 RRPUNCUXXIJQHN-UHFFFAOYSA-N 0.000 claims description 3
- CBJWZJAAOBDHHY-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-methylpyridine-2-carboxamide Chemical compound CC1=CC=CN=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 CBJWZJAAOBDHHY-UHFFFAOYSA-N 0.000 claims description 3
- KTIUYXHFYDNBTG-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-methylthiophene-2-carboxamide Chemical compound C1=CSC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=C1C KTIUYXHFYDNBTG-UHFFFAOYSA-N 0.000 claims description 3
- YGVCBNYCJDTLDY-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-3-pyridin-3-yl-1h-pyrazole-5-carboxamide Chemical compound C1=C(C=2C=NC=CC=2)NN=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 YGVCBNYCJDTLDY-UHFFFAOYSA-N 0.000 claims description 3
- UFEAOWCEBXFUNG-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-fluorobenzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 UFEAOWCEBXFUNG-UHFFFAOYSA-N 0.000 claims description 3
- NGZSLPGAWXSMDN-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-imidazo[1,2-a]pyridin-2-ylbenzamide Chemical compound C=1C=C(C=2N=C3C=CC=CN3C=2)C=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 NGZSLPGAWXSMDN-UHFFFAOYSA-N 0.000 claims description 3
- PRYPXXZPUBOHSP-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-methylbenzamide Chemical compound C1=CC(C)=CC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 PRYPXXZPUBOHSP-UHFFFAOYSA-N 0.000 claims description 3
- YPNUCBVISGAXJJ-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-methylpyridine-3-carboxamide Chemical compound CC1=CC=NC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 YPNUCBVISGAXJJ-UHFFFAOYSA-N 0.000 claims description 3
- RXZMKHLWRIOVOE-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-4-pyrazin-2-ylbenzamide Chemical compound C=1C=C(C=2N=CC=NC=2)C=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 RXZMKHLWRIOVOE-UHFFFAOYSA-N 0.000 claims description 3
- NHIKHPFLTRDPQY-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-5-methyl-1,2-oxazole-3-carboxamide Chemical compound O1C(C)=CC(C(=O)NC=2C=C3CCN(CCC3=CC=2)C2CCC2)=N1 NHIKHPFLTRDPQY-UHFFFAOYSA-N 0.000 claims description 3
- APOOQOPCGMUNEX-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-5-methylpyrazine-2-carboxamide Chemical compound C1=NC(C)=CN=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 APOOQOPCGMUNEX-UHFFFAOYSA-N 0.000 claims description 3
- TYPVNZXYMLMPIF-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-5-phenyl-1,3-oxazole-4-carboxamide Chemical compound N1=COC(C=2C=CC=CC=2)=C1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 TYPVNZXYMLMPIF-UHFFFAOYSA-N 0.000 claims description 3
- XIRLAVZGBZMOIP-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-5-pyridin-3-ylpyridine-3-carboxamide Chemical compound C=1N=CC(C=2C=NC=CC=2)=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 XIRLAVZGBZMOIP-UHFFFAOYSA-N 0.000 claims description 3
- IGUAILUEBOXOOB-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-6-methylpyridine-3-carboxamide Chemical compound C1=NC(C)=CC=C1C(=O)NC1=CC=C(CCN(CC2)C3CCC3)C2=C1 IGUAILUEBOXOOB-UHFFFAOYSA-N 0.000 claims description 3
- PHGGVUBJFJZPME-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-6-morpholin-4-ylpyridine-3-carboxamide Chemical compound C=1C=C(N2CCOCC2)N=CC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 PHGGVUBJFJZPME-UHFFFAOYSA-N 0.000 claims description 3
- TZKWBJKJTXDTOY-UHFFFAOYSA-N n-(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)-6-oxo-1h-pyridine-2-carboxamide Chemical compound C=1C=CC(=O)NC=1C(=O)NC(C=C1CC2)=CC=C1CCN2C1CCC1 TZKWBJKJTXDTOY-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/16—Benzazepines; Hydrogenated benzazepines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Anesthesiology (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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GB0329214 | 2003-12-17 | ||
GBGB0329214.1A GB0329214D0 (en) | 2003-12-17 | 2003-12-17 | Novel compounds |
PCT/EP2004/014380 WO2005058837A1 (en) | 2003-12-17 | 2004-12-15 | Benzazepine derivatives as histamine h3 antagonists |
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DE602004011401D1 DE602004011401D1 (de) | 2008-03-06 |
DE602004011401T2 true DE602004011401T2 (de) | 2008-12-24 |
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DE602004011401T Expired - Lifetime DE602004011401T2 (de) | 2003-12-17 | 2004-12-15 | Benzazepinderivate als histamin-h3-antagonisten |
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Families Citing this family (45)
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BR0317483A (pt) * | 2002-12-20 | 2005-11-16 | Glaxo Group Ltd | Derivados de benzodiazepina para o tratamento de desordens neurológicas |
JP2008502644A (ja) * | 2004-06-18 | 2008-01-31 | グラクソ グループ リミテッド | ヒスタミンh3アンタゴニストとしての3−シクロアルキルベンズアゼピン |
GB0418267D0 (en) * | 2004-08-16 | 2004-09-15 | Glaxo Group Ltd | Novel compounds |
GB0513886D0 (en) | 2005-07-06 | 2005-08-10 | Glaxo Group Ltd | Novel compounds |
DE602007011904D1 (de) | 2006-03-10 | 2011-02-24 | Neurogen Corp | Piperazinyl-oxoalkyl-tetrahydroisochinoline und verwandte analoga |
UA98772C2 (ru) | 2006-06-23 | 2012-06-25 | Эбботт Леборетриз | Производные циклопропиламина как модуляторы н3-гистаминового рецептора |
US9108948B2 (en) | 2006-06-23 | 2015-08-18 | Abbvie Inc. | Cyclopropyl amine derivatives |
CL2008000597A1 (es) * | 2007-03-01 | 2008-09-05 | Glaxo Group Ltd | Forma de dosificacion que comprende 6-(3-ciclobutil-2,3,4,5-tetrahidro-1h-benzo[d]azepin-7-il oxi)-n-metil nicotinamida, un estabilizante y un excipiente; procedimiento de preparacion; y su uso para tratar enfermedades neurologicas. |
NZ586069A (en) * | 2007-12-19 | 2012-05-25 | Amgen Inc | Fused pyridine, pyrimidine and triazine compounds as cell cycle inhibitors |
UY31736A (es) * | 2008-03-26 | 2009-11-10 | Takeda Pharmaceutical | Derivados sustituidos de pirazol y su uso |
WO2009126584A1 (en) * | 2008-04-07 | 2009-10-15 | Amgen Inc. | Gem-disubstituted and spirocyclic amino pyridines/pyrimidines as cell cycle inhibitors |
JP2011524894A (ja) | 2008-06-18 | 2011-09-08 | ファイザー・リミテッド | ニコチンアミド誘導体 |
AU2009272486A1 (en) * | 2008-07-18 | 2010-01-21 | Takeda Pharmaceutical Company Limited. | Benzazepine derivatives and their use as hstamine H3 antagonists |
PE20131197A1 (es) | 2008-10-31 | 2013-11-06 | Genentech Inc | Compuestos de pirazolopirimidina como inhibidores de jak y composiciones farmaceuticas que los contienen |
EP2410858B1 (en) * | 2009-03-23 | 2016-09-07 | Merck Sharp & Dohme Corp. | P2x3 receptor antagonists for treatment of pain |
US9186353B2 (en) | 2009-04-27 | 2015-11-17 | Abbvie Inc. | Treatment of osteoarthritis pain |
UA110324C2 (en) | 2009-07-02 | 2015-12-25 | Genentech Inc | Jak inhibitory compounds based on pyrazolo pyrimidine |
US20110172204A1 (en) | 2010-01-08 | 2011-07-14 | Takeda Pharmaceutical Company Limited | Compounds and their use |
WO2011083315A1 (en) | 2010-01-08 | 2011-07-14 | Takeda Pharmaceutical Company Limited | Compounds and their use |
WO2011083316A1 (en) | 2010-01-08 | 2011-07-14 | Takeda Pharmaceutical Company Limited | Benzazepine derivatives for the treatment of central nervous system disorders |
US20130109714A1 (en) * | 2010-03-26 | 2013-05-02 | National University Corporation Hokkaido University | Neurodegenerative disease therapeutic agent |
CA2801778C (en) | 2010-06-07 | 2018-06-05 | Novomedix, Llc | Furanyl compounds and the use thereof |
CN102985426B (zh) * | 2010-07-13 | 2015-10-07 | 弗·哈夫曼-拉罗切有限公司 | 作为irak4调节剂的吡唑并[1,5a]嘧啶和噻吩并[3,2b]嘧啶衍生物 |
US8853390B2 (en) | 2010-09-16 | 2014-10-07 | Abbvie Inc. | Processes for preparing 1,2-substituted cyclopropyl derivatives |
BR112013012078A2 (pt) * | 2010-11-15 | 2019-09-24 | Abbvie Inc | inibidores de nampt e rock |
WO2012112567A1 (en) * | 2011-02-15 | 2012-08-23 | Georgetown University | Small molecule inhibitors of agbl2 |
KR101606250B1 (ko) | 2011-03-23 | 2016-03-24 | 암젠 인크 | Cdk 4/6 및 flt3의 융합된 트리사이클릭 이중 저해제 |
WO2013151982A1 (en) | 2012-04-03 | 2013-10-10 | Arena Pharmaceuticals, Inc. | Methods and compounds useful in treating pruritus, and methods for identifying such compounds |
EP2647377A1 (en) | 2012-04-06 | 2013-10-09 | Sanofi | Use of an h3 receptor antagonist for the treatment of alzheimer's disease |
JP6293770B2 (ja) | 2012-11-05 | 2018-03-14 | ナント ホールディングス アイピー,エルエルシー | ヘッジホッグシグナル伝達経路阻害剤としての環状スルホンアミド含有誘導体 |
TWI699364B (zh) | 2014-05-23 | 2020-07-21 | 瑞士商赫孚孟拉羅股份公司 | 5-氯-2-二氟甲氧基苯基吡唑并嘧啶化合物、組合物及其使用方法 |
EP3215510B1 (en) | 2014-11-06 | 2023-06-07 | Bial-R&D Investments, S.A. | Substituted imidazo[1,5-a]pyrimidines and their use in the treatment of medical disorders |
CN107001379B (zh) | 2014-11-06 | 2022-11-01 | Bial研发投资股份有限公司 | 取代的吡唑并[1,5-a]嘧啶以及它们在治疗医学障碍中的用途 |
US20180185368A1 (en) | 2014-11-06 | 2018-07-05 | Lysosomal Therapeutics Inc. | Substituted pyrrolo[1,2-a]pyrimidines and their use in the treatment of medical disorders |
WO2017108723A2 (en) * | 2015-12-22 | 2017-06-29 | F. Hoffmann-La Roche Ag | PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS |
MX2018012208A (es) | 2016-04-06 | 2019-03-28 | Lysosomal Therapeutics Inc | Compuestos a base de imidazo [1,5-a] pirimidinil carboxamida y su uso en el tratamiento de trastornos médicos. |
WO2017176962A1 (en) | 2016-04-06 | 2017-10-12 | Lysosomal Therapeutics, Inc. | Pyrrolo[1,2-a]pyrimidinyl carboxamide compounds and their use in the treatment of medical disorders |
CA3020287A1 (en) | 2016-04-06 | 2017-10-12 | Lysosomal Therapeutics Inc. | Pyrazolo[1,5-a]pyrimidinyl carboxamide compounds and their use in the treatment of medical disorders |
EP3452455A4 (en) | 2016-05-05 | 2019-11-13 | Lysosomal Therapeutics Inc. | SUBSTITUTED IMDAZO [1,2-] PYRIDINES, SUBSTITUTED IMIDAZO [1,2-] PYRAZINES, RELATED COMPOUNDS AND THEIR USE IN THE TREATMENT OF ILLNESSES |
MX389579B (es) | 2016-05-05 | 2025-03-20 | Bial R&D Invest S A | IMIDAZO[1,2-b]PIRIDAZINAS SUSTITUIDAS, IMIDAZO[1,5-b]PIRIDAZINAS SUSTITUIDAS, COMPUESTOS RELACIONADOS Y SU USO EN EL TRATAMIENTO DE TRASTORNOS MÉDICOS |
CN109890829B (zh) | 2016-11-02 | 2022-07-15 | 豪夫迈·罗氏有限公司 | 作为IRAK4调节剂的吡唑并[1,5a]嘧啶衍生物 |
CR20190520A (es) | 2017-05-22 | 2020-01-21 | Hoffmann La Roche | Composiciones y compuestos terapéuticos y métodos para utilizarlos |
CN117126152A (zh) * | 2017-12-29 | 2023-11-28 | 生物马林药物股份有限公司 | 用于疾病治疗的乙醇酸氧化酶抑制剂 |
WO2020117877A1 (en) * | 2018-12-04 | 2020-06-11 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use |
WO2020263960A1 (en) * | 2019-06-28 | 2020-12-30 | Carl Wagner | Compositions comprising a retinoid x receptor (rxr) agonist, a retinoic acid receptor (rar) agonist, or a dual rxr/rar agonist |
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US4210749A (en) * | 1974-11-12 | 1980-07-01 | Pennwalt Corporation | Substituted 1,2,4,5-tetrahydro-3H,3 benzazepines |
DE69334150T2 (de) * | 1992-05-14 | 2008-03-13 | Baylor College Of Medicine, Houston | Mutierte steroidhormonrezeptoren, methoden für ihre benutzung und molekularer schalter für gentherapie |
US5364791A (en) * | 1992-05-14 | 1994-11-15 | Elisabetta Vegeto | Progesterone receptor having C. terminal hormone binding domain truncations |
DE4429079A1 (de) * | 1994-08-17 | 1996-02-22 | Thomae Gmbh Dr K | Cyclische Harnstoffderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
AU2001280133A1 (en) * | 2000-08-25 | 2002-03-04 | Takeda Chemical Industries Ltd. | Preventives and remedies for central nervous system diseases |
US20050090485A1 (en) * | 2002-02-13 | 2005-04-28 | Bromidge Steven M. | 7-Arylsulfonamido-2,3,4,5-tetrahydro-1h-benzo'diazepine derivatives with 5ht6 receptor affinity for the reatment of cns disorders |
GB0210762D0 (en) * | 2002-05-10 | 2002-06-19 | Glaxo Group Ltd | Compounds |
BR0317483A (pt) * | 2002-12-20 | 2005-11-16 | Glaxo Group Ltd | Derivados de benzodiazepina para o tratamento de desordens neurológicas |
-
2003
- 2003-12-17 GB GBGB0329214.1A patent/GB0329214D0/en not_active Ceased
-
2004
- 2004-12-15 WO PCT/EP2004/014380 patent/WO2005058837A1/en active IP Right Grant
- 2004-12-15 JP JP2006544347A patent/JP2007514690A/ja active Pending
- 2004-12-15 US US10/596,503 patent/US20070060566A1/en not_active Abandoned
- 2004-12-15 ES ES04803989T patent/ES2299896T3/es not_active Expired - Lifetime
- 2004-12-15 EP EP04803989A patent/EP1713778B1/en not_active Expired - Lifetime
- 2004-12-15 AT AT04803989T patent/ATE384050T1/de not_active IP Right Cessation
- 2004-12-15 DE DE602004011401T patent/DE602004011401T2/de not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
ATE384050T1 (de) | 2008-02-15 |
DE602004011401D1 (de) | 2008-03-06 |
ES2299896T3 (es) | 2008-06-01 |
US20070060566A1 (en) | 2007-03-15 |
WO2005058837A1 (en) | 2005-06-30 |
EP1713778B1 (en) | 2008-01-16 |
EP1713778A1 (en) | 2006-10-25 |
JP2007514690A (ja) | 2007-06-07 |
GB0329214D0 (en) | 2004-01-21 |
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